Imperial College London
Portrait Picture

DrJunIshihara

Faculty of Engineering, Department of Bioengineering

Lecturer
 
 
 
//

Contact

 

j.ishihara Website CV

 
 
//

Location

 

86 Woodlane London W12 0BZSir Michael Uren HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Yuba:2021:10.1002/art.41585,
author = {Yuba, E and Budina, E and Katsumata, K and Ishihara, A and Mansurov, A and Alpar, AT and Watkins, EA and Hosseinchi, P and Reda, JW and Lauterbach, AL and Nguyen, M and Solanki, A and Kageyama, T and Swartz, MA and Ishihara, J and Hubbell, JA},
doi = {10.1002/art.41585},
journal = {Arthritis & Rheumatology},
pages = {769--778},
title = {Enhanced lymph node trafficking of engineered IL10 suppresses rheumatoid arthritis in murine models},
url = {http://dx.doi.org/10.1002/art.41585},
volume = {73},
year = {2021}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectiveRheumatoid arthritis (RA) is a major autoimmune disease that causes synovitis and joint damage. Although clinical trials using interleukin10 (IL10), an antiinflammatory cytokine, have been performed as a potential treatment of RA, its therapeutic effects have been limited, potentially due to insufficient residence in lymphoid organs, where antigen recognition primarily occurs. Here, we engineered IL10 as a fusion with serum albumin (SA).MethodsSAfused IL10 was recombinantly expressed. After intravenous injection to mice, retention of SAIL10 at lymph node (LN), immune cell compositions at paws, and therapeutic effect on arthritis model mice were assessed.ResultsSA fusion to IL10 led to enhanced LN accumulation compared with unmodified IL10. Intravenous SAIL10 treatment restored immune cell composition in the paws to a normal status, elevated the frequency of suppressive M2 macrophages, reduced IL17A amount in the pawdraining LN, and protected joint morphology. Intravenous SAIL10 treatment showed similar efficacy as treatment with an antiTNFα antibody. SAIL10 was equally effective when administered intravenously, locally or subcutaneously, which benefits clinical translation of this molecule.ConclusionSA fusion to IL10 is a simple but effective engineering strategy for RA therapy and holds clinical translational potential.
AU  - Yuba,E
AU  - Budina,E
AU  - Katsumata,K
AU  - Ishihara,A
AU  - Mansurov,A
AU  - Alpar,AT
AU  - Watkins,EA
AU  - Hosseinchi,P
AU  - Reda,JW
AU  - Lauterbach,AL
AU  - Nguyen,M
AU  - Solanki,A
AU  - Kageyama,T
AU  - Swartz,MA
AU  - Ishihara,J
AU  - Hubbell,JA
DO  - 10.1002/art.41585
EP  - 778
PY  - 2021///
SN  - 2326-5191
SP  - 769
TI  - Enhanced lymph node trafficking of engineered IL10 suppresses rheumatoid arthritis in murine models
T2  - Arthritis & Rheumatology
UR  - http://dx.doi.org/10.1002/art.41585
UR  - https://onlinelibrary.wiley.com/doi/10.1002/art.41585
UR  - http://hdl.handle.net/10044/1/84611
VL  - 73
ER  -
Download